PROJECT SUMMARY ABSTRACT Combustible tobacco products, primarily cigarettes, are the single greatest cause of cancer in the U.S. Cessation of all tobacco products would have an indisputably large impact on U.S. cancer rates; however, simulation models indicate that a significant benefit over the next two decades will occur if adult smokers switch to electronic nicotine delivery systems (ENDS) as a complete substitute for combustible tobacco products. Research has identified that uncertainty and misperceptions about the health risks and benefits of ENDS, as well as consumer dissatisfaction with product characteristics, limit initiation and complete substitution for combustible cigarettes. The objective of this project is to address the critical need for timely evidence evaluating how price, indoor-air policies, and ENDS product characteristics (product type and design, flavors, ability to reduce cravings to smoke) interact with risk/benefit perceptions to affect smokers? decisions to reject the products, to substitute them for only a few cigarettes, to switch exclusively to these products, or to use ENDS to completely quit using tobacco products. Guided by a conceptual framework, Aim 1 will involve qualitative focus-group interviews of 120 current/former adult smokers, and an intensive assessment over 1 year (12 weekly, then 3 quarterly) with 300 current smokers who recently initiated ENDS use to examine how ENDS product characteristics influence smokers? decisions to initiate, dual use with, or substitute for their use of combustible tobacco products. In the intensive longitudinal study, a piecewise, dynamic latent class analysis will test hypotheses regarding the effects of product characteristics and the dynamic interplay of contextual factors, cognitive and affective decision-making processes, tobacco use, and experiences in shaping patterns and trajectories of tobacco use. In Aim 2, two behavioral experiments and a randomized clinical trial will be conducted. A discrete-choice experiment (DCE) will be embedded in the baseline survey of the intensive longitudinal study of 300 current smokers to examine the relative importance of ENDS product characteristics on risk/benefit perceptions; product preferences, and intentions for use, and evaluate the predictive validity of these preferences on future tobacco use and patterns. A second DCE will examine the interaction of product characteristics, risk/benefit perceptions, and contextual factors (e.g., whether products can be used where smoking is prohibited) on smokers? preferences for the product with a nationally representative sample of 2400 adult current smokers who currently, formerly, or never used ENDS/Heat-not-Burn(HnB) products. These results will inform the experimental manipulations in an innovative hypothetical purchase task (HPT) paradigm with a nationally representative sample of 1800 adult smokers stratified by their prior experience with ENDS/HnB. This randomized clinical trial will manipulate risk/benefit perceptions of ENDS/HnB products to estimate the effect on smokers? consumption (demand) of conventional cigarettes, ENDS, and HnB, including the substitutability or complementarity of ENDS and HnB for each other and for combustible cigarettes controlling for decision-making biases, perceived addiction, and contextual factors.